More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages.
U.S. Pat. No. 4,464,376, issued to A. Sunshine et al., on Aug. 7, 1984 describes analgesic and antiinflammatory compositions which comprise caffeine together with a selected non-narcotic/non-steroidal antiinflammatory drug (NSAID) or a selected narcotic analgesic or both. This patent discloses that the analgesic effect of the combination of a selected NSAID and a selected narcotic analgesic is greater than for either alone which analgesic effect is further enhanced by the addition of caffeine. Sunshine provides no evidence or suggestion of other than an additive analgesic effect for the combinations.
S. Cooper et al., Pharmacotherapy, 2, 162 (1982), describe the analgesic efficacy of an ibuprofen/codeine combination in patients who had undergone dental impaction surgery. Codeine was found to add "a small amount of additional analgesia when used in combination with ibuprofen." This increase in analgesic effects was not statistically significant and there is no suggestion that the combination had a synergistic effect.
U.S. Pat. No. 4,237,140, issued to J. R. Dudzinski on Dec. 2, 1980, describes an analgesic mixture of nalbuphine and acetaminophen. U.S. Pat. No. 4,282,215, issued to J. R. Dudzinski and W. K. Schmidt on Aug. 4, 1981, describes an analgesic mixture of nalbuphine and aspirin. Other nalbuphine analgesic combinations are described in U.S. Pat. No. 4,366,159, issued to M. R. Magruder on Dec. 28, 1982 (with narcotics); U.S. Pat. No. 4,404,210, issued to W. K. Schmidt on Sept. 13, 1983 (with ibuprofen); U.S. Pat. No. 4,407,805, issued to W. K. Schmidt on Oct. 4, 1983 (zomepirac); U.S. Pat. No. 4,402,962, issued to W. K. Schmidt on Sept. 6, 1983 (4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole); U.S. Pat. No. 4,407,804, issued to W. K. Schmidt on Oct. 4, 1983 (indomethacin); U.S. Pat. No. 4,404,208, issued to W. K. Schmidt on Sept. 13, 1983 (tiflamizole); U.S. Pat. No. 4,404,209, issued to W. K. Schmidt on Sept. 13, 1983 (sulindac); and U.S. Pat. No. 4,404,211, issued to W. K. Schmidt on Sept. 13, 1983 (flurbiprofen).
U.S. Pat. Nos. 3,228,831 and 3,385,886 issued to Nicholson and Adams disclose the synthesis, formulation, and analgesic properties of .alpha.-methyl-4-(2-methylpropyl)benzeneacetic acid, commonly called ibuprofen: ##STR1## Adams et al., Arch. Pharmacodyn. Ther., 178, 115 (1969), further characterize the use of ibuprofen as an analgesic.
Narcotic analgesics are well known, strong analgesics which can, unfortunately, be addictive and subjected to abuse by parenteral administration. A continuing goal is to be able to reduce the dosage of such narcotic analgesics by combining them with non-addicting ingredients while still maintaining a high level of analgesia.